Preterm intraventricular haemorrhage - Effects of extracellular haemoglobin

Intraventricular haemorrhage (IVH) is the most common brain lesion in preterm infants and is most commonly seen in the sickest children, with 15-20% of very preterm infants developing IVH. The mortality of infants with severe IVH is 20-50 % in the neonatal period and over 50 % of surviving infants develop post-haemorrhagic ventricular dilatation (PHVD) and 40-80 % develop severe neurological impairment, mainly cerebral palsy and mental retardation. To date there is no available therapy to prevent infants from developing either hydrocephalus or serious neurological disability. Infants who develop hydrocephalus receive a life-long ventriculo-peritoneal shunt, which is an efficient means of preventing ventricular distension but does not reduce neurological impairment. Mechanisms leading to brain damage and hydrocephalus following IVH are complex and incompletely understood. However, inflammation and oxidative stress have been identified as two major culprits leading to irreversible damage in the vulnerable immature periventricular brain matter. Dysfunction of cerebrospinal fluid (CSF) production contributes to the development of PHVD but the exact molecular mechanisms remain unknown. The choroid plexus, which produces the CSF, is adjacent to the origin of IVH and is the first organ to encounter the extravasated blood. The subsequent haemolysis of red blood cells causes release of cell-free haemoglobin (Hb), which will with time further degrade releasing the toxic substances hemin, free iron, and various ROS (reactive oxygen species). Metabolites of cell-free Hb have been identified as an initiator of inflammation in the context of adult cerebral haemorrhage and inflammation of the ependyma has been shown to cause alterations of the blood-brain barrier (BBB). Our working hypothesis is that cell-free Hb and its metabolites act as causal initiators of inflammation following IVH, constituting a critical up-stream event eventually leading to periventricular cell death. We further hypothesize that inflammation of the choroid plexus alters the ability of the epithelium to maintain CSF homeostasis contributing to the formation of post-haemorrhagic hydrocephalus. To test the hypothesis we used the rabbit pup model of preterm IVH. It is excellently suited since rabbit pups have a germinal matrix with vulnerable capillary meshwork prone to rupture and have CNS maturation comparable to a 28-30 weeks preterm human infant. The application of high-frequency ultrasound enabled accurate measurements of haemorrhagic size and distension as well as ultrasound guided intraventricular injections and CSF sampling. Following IVH there is a release of free haemoglobin in its reduced form, oxyHb, into the intraventricular space. OxyHb autooxidises to metHb over time and the concentration of the key inflammatory cytokine TNF-α is highly correlated to that of metHb. In an astrocyte cell culture, metHb induces TNF-α production whereas oxyHb does not. We therefore conclude that the formation of metHb is a key up-stream event leading to inflammation following IVH. Following IVH there is extensive damage to the choroid plexus epithelium, which develops over time. There is a distinct inflammatory and cellular response induced by haemoglobin metabolites. Injection or co-incubation with haptoglobin, a haemoglobin scavenger, reduces or reverses the effects of haemoglobin both in vivo and in vitro. Aquaporins (AQP) are water transporting transmembrane proteins playing a central role in CSF production. Following IVH the expression of AQP1, the key AQP in the choroid plexus, is down-regulated whereas the expression of AQP5, not previously described in the choroid plexus, is up-regulated. This probably represents an adaptive response to insult and might be of importance in understanding the development of PHVD. In conclusion; following IVH released cell free haemoglobin, metabolized to metHb and hemin, constitutes a causal up-stream initiator of inflammation and cellular damage. Scavenging or removal of haemoglobin might be an efficient and feasible approach to reduce brain damage following preterm IVH

Venous thromboembolism with special focus on genetic and potential acquired risk factors

Venous thromboembolism (VTE) is a relatively common cause of morbidity and mortality. It has an annual incidence of around 0.1- 0.3%. It is a multifactorial disease with many known risk factors, both transient and persistent. Among these, several genetic risk factors have been described. The most common genetic risk factor, factor V Leiden mutation in heterozygote form, is found in 5-8% of the Caucasian population. Although much is known about the VTE disease, evaluating the recurrence risk, duration and risk of the anticoagulation therapy remains a challenge and many questions are still unanswered. The aims of this thesis are to evaluate the distribution and clinical impact of the most common inherited risk factors for VTE in a population based total material from southern Sweden as well as estimating heterozygous FVL mutation as a risk factor for VTE recurrence. Furthermore, to look into other potential acquired risk factors for VT, such as inflammation in a male cohort from a screening program and, finally, evaluate the risk for bleeding in relation to renal function within VTE patients on warfarin treatment in a cohort from a Swedish national quality registry for anticoagulation (AuriculA). The prevalence of the FVL mutation in heterozygous form was found in approximately one fourth of the VTE patients and increased the risk for recurrence significantly, by 2-3 fold. The mutation in homozygous form is much less frequent but these patients had a higher average age at first thrombosis than many studies previously described. Furthermore, homozygous women were affected at an earlier age compared to men and female controls and it appeared that thrombi in homozygous FVL were more prone to be in the lower extremity. The odds ratio for thrombosis was lower than previously described. The risk for VTE in relation to the number of raised inflammatory specific proteins (ISPs), i.e. fibrinogen, haptoglobin, ceruloplasmin, alfa-1-antitrypsin and orosomucoid, as well as individual ISPs was not significantly increased. However, age, BMI and diabetes mellitus type 2 were significant risk factors for developing a VTE. On the other hand, factors such as cholesterol, triglycerides, blood pressure and smoking were not. VTE patients on anticoagulation treatment with warfarin seemed to be younger, and hence had a better renal function, than patients with other indications for warfarin therapy. Among those VTE patients there was not significantly increased bleeding with impaired renal function, although a trend could be seen

Meeting in the Middle: Using Stakeholder Theory to Create Shared Value as a Way of Increasing CSR Implementation amongst SMEs – An Icelandic Perspective

The purpose of this thesis is to explore SMEs’ relations to stakeholders when implementing corporate social responsibility. Furthermore, it examines what role the size of the SMEs play in implementing CSR and in managing stakeholders. The thesis explores whether the competitive landscape of the market creates tension where SMEs’ decision makers feel pressured to choose between doing well financially and socially. Additionally, the thesis aims to find a solution that will engage SMEs to partake in CSR to a greater extent by utilizing stakeholder theory and the notion of creating shared value. This thesis helps bridge the gap of low CSR implementation rate in SMEs and finds that increasing awareness of impact is a key aspect of increasing implementation along with addressing the most important motivation for CSR implementation, the altruistic motivation. Furthermore, this thesis suggests that CSR implementation in SMEs could be improved by combining stakeholder theory with the notion of creating shared value. Our findings identify four key networking tools that could assist in doing so through the implementation of the framework we have created based on these findings, the SME Network System

Women's attitudes to hormone replacement therapy in the aftermath of the Women's Health Initiative study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAIM: This paper is a report of a study conducted in 2004 on the determinants of attitudes towards hormone replacement therapy in the aftermath of the report on the findings of the Women's Health Initiative study. BACKGROUND: The unexpected findings of the Women's Health Initiative study, published in July 2002, showed that the risk of using combined hormones exceeded their benefits. This complicated women's decision-making about hormone use and made it important to study the determinants of their attitudes to hormone therapy, as these are likely to influence their behaviour. METHODS: A cross-sectional design was conducted with a sample of 561 women drawn from the National Registry of Iceland. A self-administered questionnaire, measuring attitudes towards hormone replacement therapy, attitudes towards menopause, extent and source of menopausal education, symptom experience, health and lifestyle and knowledge about the findings of the Women's Health Initiative, was used. The overall response rate was 56%. Attitudes to hormone replacement therapy were compared using anova, t-tests and correlations. RESULTS: Participants generally had positive attitudes. Knowledge about the Women's Health Initiative study was not associated with more negative attitudes. However, receiving the information from and discussing it with a doctor were associated with more positive attitudes. Positive attitudes towards hormone therapy were also associated with higher age, time since last menstrual period and current use of hormone replacement therapy. Negative attitudes were associated with use of natural remedies and receiving information from or discussing hormone therapy with family or friends. CONCLUSION: Research is needed to identify the dynamics of the medical interview, and the nature of input from friends, spouse and other family members. The content of these messages may be different and conflicting, for example, between doctors and family members. The nature of this conflict and conflicts of interests need to be identified in order to inform women's decision-making. In addition, action needs to be taken in order to strengthen the advisory role of nurses

Self-assessed occupational health and working environment of female nurses, cabin crew and teachers

To access Publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAIM: The aim of this study was to describe and compare the self-assessed occupational health among female nurses, cabin crew and teachers, in relation to their working environment. Background: Similarities between the three occupations, i.e. predominantly female and service-oriented, render them interesting in comparison with respect to health and working environment. METHODS: The participants were female Icelandic cabin crew, nurses and elementary school teachers. A questionnaire including items on socio-demographics, working environment (addressing work pace, job security, monotonous work, assistance, physically strenuous work and physical environmental factors) and a symptom list was used for data collection. Factor analyses on the symptom list resulted in five symptom scales: Musculoskeletal, Stress and exhaustion, Common cold, Gastrointestinal and Sound perception scale. A total of 1571 questionnaires were distributed. The response rate was 65.7-69%, depending on occupation. Data were collected in 2002. RESULTS: Cabin crew reported worse gastrointestinal, sound perception and common cold symptoms than nurses and teachers. Cabin crew and teachers reported worse symptoms of stress and exhaustion than nurses (p < 0.05). When compared with teachers and nurses cabin crew reported less job security and more physically strenuous and monotonous work. Nurses were likelier to seek assistance from co-workers or patients as well as to take care of an older relative than teachers and cabin crew. Regression analysis found that within each occupation distress from environmental factors resulted in higher score on all the symptom scales. CONCLUSIONS: Nurses experience less stress and exhaustion than teachers and cabin crew. In comparison with one or both of the other occupations nurses are more likely to assist each other with their work, experience job security, reporting physically complex work and take care of older relatives. This should be highlighted as positive aspects of nurses' work praised as displaying responsibility and interconnectedness of nurses'

Assessing the Role of Cognitive Behavioral Therapy in the Management of Chronic Nonspecific Back Pain

Purpose: The aim of this study is to provide a narrative review of the current state of knowledge of the role of cognitive behavioral therapy (CBT) in the management of chronic nonspecific back pain. Methods: A literature search on all studies published up until July 2012 (PubMed and PsycINFO) was performed. The search string consisted of 4 steps: cognitive behavioral therapy/treatment/management/modification/intervention, chronic, back pain (MeSH term) or low back pain (MeSH term), and randomized controlled trial (MeSH term). The conclusions are based on the results from randomized controlled trials (RCTs) and reviews of RCTs. Interventions were not required to be pure CBT interventions, but were required to include both cognitive and behavioral components. Results: The search yielded 108 studies, with 46 included in the analysis. Eligible intervention studies were categorized as CBT compared to wait-list controls/treatment as usual, physical treatments/exercise, information/education, biofeedback, operant behavioral treatment, lumbar spinal fusion surgery, and relaxation training. The results showed that CBT is a beneficial treatment for chronic back pain on a wide range of relevant variables, especially when compared to wait-list controls/treatment as usual. With regards to the other comparison treatments, results were mixed and inconclusive. Conclusion: The results of this review suggest that CBT is a beneficial treatment for chronic nonspecific back pain, leading to improvements in a wide range of relevant cognitive, behavioral and physical variables. This is especially evident when CBT is compared to treatment as usual or wait-list controls, but mixed and inconclusive when compared with various other treatments. Multidisciplinary and transdisciplinary interventions that integrate CBT with other approaches may represent the future direction of management of chronic back pain, with treatments modified for specific circumstances and stakeholders. There is a need for future intervention studies to be specific in their use of cognitive behavioral elements, in order for results to be comparable

An Analysis of Open Science Policies in Europe, v6

This report is the sixth in a series of SPARC Europe and DCC analyses of national Open Science policies in Europe and covers the period between March 2020 and August 2020. This issue provides an update on activity across European Member States and relevant countries from the European Research Area. This issue includes a section on policy change related to Covid-19 and an overview of European Open Science Cloud (EOSC) policy-related activities among the European Commission supported INFRAEOSC 5b projects. To access previous versions of the analysis of Open Data and Open Science policies in Europe and other SPARC Europe reports related to Open Data please see https://sparceurope.org/what-we-do/open-data/sparc-europe-open-data-resources/

Підвищення ефективності теплопостачання при врахуванні температурно-погодних факторів

In this paper we will address the questions of what and where the value of open access to research data might be and how libraries and related stakeholders can contribute to achieve the benefits of freely sharing data. In particular, the emphasis is on how libraries need to acquire the competence for collaboration to train and encourage researchers and library staff to work with open data. The paper is based on the early results of the RECODE project, an EU FP7 project that addresses the drivers and barriers in developing open access to research data in Europe (http://www.recodeproject.eu)

Virtual identity as practice : exploring the relationship between role-players and their characters in the massively multiplayer online game 'Star Wars Galaxies'

The objective of this research is firstly, to evaluate claims that cyberspace, due to its inherent qualities, has had an unprecedented effect on how we construct, present and think about our collective and individual identities online and offline. Secondly, it will highlight how people use shared understandings of popular culture products in order to maintain social formations in cyberspace.EThOS - Electronic Theses Online ServiceGBUnited Kingdo